This work is investigating several aspects of pancreatic islet transplantation in animals. During the past year we have made comparative studies of the susceptibility to rejection of allogeneic islets transplanted as free grafts versus islets transplanted as part of immediately vascularized segmental grafts, under conditions in which the beta cell mass transplanted, as judged by tissue insulin content, was equivalent. Rejection, as defined as recurrence of hyperglycemia, occurs more rapidly after transplantation of islets, but the difference could still be due to a nonimmune quantitative factors since in isograft controls, the final beta cell mass that became engrafted after transplantation, as judged by tissue insulin content, ranged from 51 to 73%. We have also investigated the use of cyclosporin A to prevent the rejection of both pancreas and islet grafts in rats and have found it to be the most effective agent we have so far tested. We have performed further experiments on preservation of pancreatic islets and have found that segmental pancreatic grafts from dogs could be stored for 24 hours in Collins solution with good physiological function after transplantation. This technique will now be applied to dispersed pancreatic islets prepared from stored pancreatic segments. Other areas of our investigation include investigation of alternative techniques for dispersion of pancreatic islets for transplantation, pancreas and islet transplantation in spontaneous diabetes in dogs, in comparison of the metabolic efficiency of immediately vascularized segmental pancreatic grafts and free grafts of islets. The major thrust of our ongoing experiments is the investigation of immunological approaches to prevent the rejection of allogeneic islets.